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Brazilian Journal of Microbiology :... Sep 2023Neuroprotection is one of the important protection methods against neuronal cells and tissue damage caused by neurodegenerative diseases such as Alzheimer's,... (Review)
Review
Neuroprotection is one of the important protection methods against neuronal cells and tissue damage caused by neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and multiple sclerosis. Various bioactive compounds produced by medicinal plants can potentially treat central nervous system (CNS) disorders. Apart from these resources, endophytes also produce diverse secondary metabolites capable of protecting the CNS. The bioactive compounds produced by endophytes play essential roles in enhancing the growth factors, antioxidant defence functions, diminishing neuroinflammatory, and apoptotic pathways. The efficacy of compounds produced by endophytic fungi was also evaluated by enzymes, cell lines, and in vivo models. Acetylcholine esterase (AChE) inhibition is frequently used to assess in vitro neuroprotective activity along with cytotoxicity-induced neuronal cell lines. Some of drugs, such as tacrine, donepezil, rivastigmine, galantamine, and other compounds, are generally used as reference standards. Furthermore, clinical trials are required to confirm the role of these natural compounds in neuroprotection efficacy and evaluate their safety profile. This review illustrates the production of various bioactive compounds produced by endophytic fungi and their role in preventing neurodegeneration.
Topics: Humans; Plants, Medicinal; Donepezil; Rivastigmine; Endophytes; Fungi; Central Nervous System Diseases
PubMed: 37165297
DOI: 10.1007/s42770-023-00997-1 -
European Journal of Cancer Care May 2019Many patients with brain cancer experience cognitive problems. In this narrative review, we comprehensively evaluated empirical studies on various intervention... (Review)
Review
INTRODUCTION
Many patients with brain cancer experience cognitive problems. In this narrative review, we comprehensively evaluated empirical studies on various intervention approaches for cognitive problems in these patients.
METHODS
Intervention studies that reported effects on cognitive functioning (either objectively tested or subjectively reported) in adult patients with primary and/or secondary brain tumours were identified through online searches in PubMed (MEDLINE) and Web of Science up to 13 March 2019.
RESULTS
Of the 364 identified records, 10 pharmacological (including five randomised placebo-controlled trials), 10 cognitive rehabilitation (including five [pilot] RCTs) and two multiple-group exercise studies matched the inclusion criteria. Seventeen of 22 studies had final sample sizes smaller than 40. Several cognitive rehabilitation studies and some pharmacological approaches (donepezil and memantine) showed (at least partial) benefits for cognitive problems in adults with brain cancer. The effects of other pharmacological and exercise interventions were inconclusive and/or preliminary.
CONCLUSION
Overall, drawing firm conclusions is complicated due to various methodological shortcomings, including the absence of a (placebo) control group and small sample sizes. Promising effects have been reported for cognitive rehabilitation and some pharmacological approaches. Suggestions for more thorough research with respect to the various approaches are provided.
Topics: Brain Neoplasms; Central Nervous System Stimulants; Cholinesterase Inhibitors; Cognition; Cognitive Dysfunction; Cognitive Remediation; Donepezil; Dopamine Agents; Exercise; Ginkgo biloba; Humans; Memantine; Plant Extracts
PubMed: 31090162
DOI: 10.1111/ecc.13088 -
Revista de Saude Publica 2023To analyze the consumption of drugs for Alzheimer's disease on the Brazilian private market and its geographical distribution from 2014 to 2020.
OBJECTIVE
To analyze the consumption of drugs for Alzheimer's disease on the Brazilian private market and its geographical distribution from 2014 to 2020.
METHODS
National data from the Brazilian National System of Controlled Product Management were used, regarding sales of donepezil, galantamine, rivastigmine, and memantine from January 2014 to December 2020. Sales data were used as a proxy for drug consumption and expressed as defined daily dose/1,000 inhabitants/year at national, regional, federative unit and microregion levels.
RESULTS
Drug consumption went from 5,000 defined daily doses/1,000 inhabitants, in 2014, to more than 16,000/1,000 inhabitants, in 2020, and all federative units showed positive variation. The Brazilian Northeast had the highest cumulative consumption in the period but displayed microregional disparities while the North region had the lowest consumption. Donepezil and memantine were the most consumed drugs, with the highest growth in consumption from 2014 to 2020.
CONCLUSION
The consumption of medicines indicated to treat Alzheimer's disease tripled in Brazil between 2014 and 2020, which may relate to the increase in the prevalence of the disease in the country, greater access to health services, and inappropriate use. This challenges managers and healthcare providers due to population aging and the increased prevalence of chronic-degenerative diseases.
Topics: Humans; Alzheimer Disease; Donepezil; Memantine; Brazil; Cholinesterase Inhibitors; Piperidines; Phenylcarbamates; Indans
PubMed: 37971177
DOI: 10.11606/s1518-8787.2023057005128 -
Dementia and Geriatric Cognitive... 2016The 'Asia-Pacific Expert Panel (APEX) for donepezil 23 mg' met in November 2015 to review evidence for the recently approved high dose of donepezil and to provide... (Review)
Review
BACKGROUND
The 'Asia-Pacific Expert Panel (APEX) for donepezil 23 mg' met in November 2015 to review evidence for the recently approved high dose of donepezil and to provide recommendations to help physicians in Asia make informed clinical decisions about using donepezil 23 mg in patients with moderate-to-severe Alzheimer's disease (AD).
SUMMARY
In a global phase III study (study 326) in patients with moderate-to-severe AD, donepezil 23 mg/day demonstrated significantly greater cognitive benefits versus donepezil 10 mg/day, with a between-treatment difference in mean change in the Severe Impairment Battery score of 2.2 points (p < 0.001) in the overall population and 3.1 points (p < 0.001) in patients with advanced AD. A subanalysis of study 326 demonstrated that the benefits and risks associated with donepezil 23 mg/day versus donepezil 10 mg/day in Asian patients with moderate-to-severe AD were comparable to those in the global study population.
KEY MESSAGE
Donepezil 23 mg is a valuable treatment for patients with AD, particularly those with advanced disease. The APEX emphasized the importance of patient selection (AD severity, tolerability of lower doses of donepezil, and absence of contraindications), a stepwise titration strategy for dose escalation, and appropriate monitoring and counseling of patients and caregivers in the management of patients with AD.
PubMed: 27703471
DOI: 10.1159/000448214 -
Communications Medicine May 2024Alzheimer's disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be...
BACKGROUND
Alzheimer's disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival.
METHODS
We conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer's disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. Also, we formally tested for the presence of interaction between these drugs.
RESULTS
Here, we show that the combined use of Donepezil and Memantine significantly elevates the probability of five-year survival. In particular, their combined use increases the probability of five-year survival by 0.050 (0.021, 0.078) (6.4%), 0.049 (0.012, 0.085), (6.3%), 0.065 (0.035, 0.095) (8.3%) compared to no drug treatment, the Memantine monotherapy, and the Donepezil monotherapy respectively. We also identify a significant beneficial additive drug-drug interaction effect between Donepezil and Memantine of 0.064 (0.030, 0.098).
CONCLUSIONS
Based on our findings, adopting combined treatment of Memantine and Donepezil could extend the lives of approximately 303,000 people with AD living in the USA to be beyond five-years from diagnosis. If these patients instead have no drug treatment, Memantine monotherapy or Donepezil monotherapy they would be expected to die within five years.
PubMed: 38783011
DOI: 10.1038/s43856-024-00527-6 -
Journal of Alzheimer's Disease : JAD 2022Donepezil is frequently used to treat Alzheimer's disease (AD) symptoms but is associated with early discontinuation. Determining the persistence rates of anti-dementia...
BACKGROUND
Donepezil is frequently used to treat Alzheimer's disease (AD) symptoms but is associated with early discontinuation. Determining the persistence rates of anti-dementia drug use after donepezil initiation may inform the development and improvement of treatment strategies, but there is little evidence from Japan.
OBJECTIVE
To determine anti-dementia drug persistence following donepezil initiation among AD patients in Japan using insurance claims data.
METHODS
Insurance claims data for AD patients with newly prescribed donepezil were obtained from 17 municipalities between April 2014 and October 2021. Anti-dementia drug persistence was defined as a gap of ≤60 days between the last donepezil prescription and a subsequent prescription of donepezil, another cholinesterase inhibitor, or memantine. Cox proportional hazards models were used to analyze the association between care needs levels and discontinuation.
RESULTS
We analyzed 20,474 AD patients (mean age±standard deviation: 82.2±6.3 years, women: 65.7%). The persistence rates were 89.1% at 30 days, 79.4% at 90 days, 72.6% at 180 days, 64.5% at 360 days, and 58.3% at 540 days after initiation. Among the care needs levels, the hazard ratio (95% confidence interval) for discontinuation was 1.01 (0.94-1.07) for patients with support needs, 1.12 (1.06-1.18) for patients with low long-term care needs, and 1.31 (1.21-1.40) for patients with moderate-to-high long-term care needs relative to independent patients.
CONCLUSION
Japanese AD patients demonstrated low anti-dementia drug persistence rates that were similar to those of other countries. Higher long-term care needs were associated with discontinuation. Further measures are needed to improve drug persistence in AD patients.
Topics: Humans; Female; Aged; Aged, 80 and over; Donepezil; Cholinesterase Inhibitors; Alzheimer Disease; Japan; Indans; Piperidines
PubMed: 36213993
DOI: 10.3233/JAD-220200 -
Journal of Enzyme Inhibition and... Dec 2023Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The...
Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid-donepezil-rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that was a reversible and selective BChE inhibitor (IC = 0.53 μM), and the docking provided the possible mechanism. Compound also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, was a potential multifunctional lead compound against AD.
Topics: Humans; Aged; Donepezil; Rivastigmine; Alzheimer Disease; Cholinesterase Inhibitors; Neuroprotective Agents; Acetylcholinesterase; Structure-Activity Relationship
PubMed: 37414563
DOI: 10.1080/14756366.2023.2231661 -
Stroke Oct 2015Among the therapeutic strategies under study to improve long-term outcome after stroke are drugs targeting events that underlie recovery. Drugs that enhance recovery are... (Review)
Review
Among the therapeutic strategies under study to improve long-term outcome after stroke are drugs targeting events that underlie recovery. Drugs that enhance recovery are separate from those that promote neuroprotection or reperfusion in patients with stroke. Recovery-based drugs have distinct therapeutic targets that are related to plasticity and growth following stroke, and in general, improvements in behavioral outcome are not accompanied by a reduction in infarct volume. Interventions targeting recovery have a time window measured in days or sometimes weeks-months, suggesting potential utility for a large percentage of patients with stroke. Currently, among drugs that enhance motor recovery after stroke in humans, the strongest evidence exists for serotonergic and dopaminergic agents. Restorative therapies generally target the brain directly, in contrast to approved stroke therapeutics that target arteries, clots, platelets, glucose, or cholesterol. Targeting the brain has wide-ranging implications, for example, in relation to drug delivery. In addition, because restorative drugs aim to change brain structure and function, their effects are influenced by concomitant behavioral experience, a finding that informs selection of entry criteria, outcome measures, and biomarkers in a clinical trial setting. These points underscore the importance of a neural systems approach in studying stroke recovery.
Topics: Cholinesterase Inhibitors; Donepezil; Dopamine Agents; Humans; Indans; Levodopa; Motor Activity; Motor Skills; Piperidines; Recovery of Function; Selective Serotonin Reuptake Inhibitors; Stroke; Stroke Rehabilitation
PubMed: 26265126
DOI: 10.1161/STROKEAHA.115.007433 -
Drugs & Aging Nov 2023The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia.
OBJECTIVES
While these drugs are known to induce classic cholinergic adverse events such as diarrhea, their potential to cause psychiatric adverse events has yet to be thoroughly examined.
METHODS
We sought to determine the risk of psychiatric adverse events associated with the use of AChEIs through a systematic review and meta-analysis of double-blind randomized controlled trials involving patients with Alzheimer's dementia and Parkinson's dementia.
RESULTS
A total of 48 trials encompassing 22,845 patients were included in our analysis. Anorexia was the most commonly reported psychiatric adverse event, followed by agitation, insomnia, and depression. Individuals exposed to AChEIs had a greater risk of experiencing appetite disorders, insomnia, or depression compared with those who received placebo (anorexia: odds ratio [OR] 2.93, 95% confidence interval [CI] 2.29-3.75; p < 0.00001; decreased appetite: OR 1.93, 95% CI 1.33-2.82; p = 0.0006; insomnia: OR 1.55, 95% CI 1.25-1.93; p < 0.0001; and depression: OR 1.59, 95% CI 1.23-2.06, p = 0.0004). Appetite disorders were also more frequent with high-dose versus low-dose therapy. A subgroup analysis revealed that the risk of insomnia was higher for donepezil than for galantamine.
CONCLUSIONS
Our findings suggest that AChEI therapy may negatively impact psychological health, and careful monitoring of new psychiatric symptoms is warranted. Lowering the dose may resolve some psychiatric adverse events, as may switching to galantamine in the case of insomnia.
CLINICAL TRIAL REGISTRATION
The study was pre-registered on PROSPERO (CRD42021258376).
Topics: Humans; Acetylcholinesterase; Alzheimer Disease; Anorexia; Cholinesterase Inhibitors; Donepezil; Galantamine; Parkinson Disease; Phenylcarbamates; Randomized Controlled Trials as Topic; Rivastigmine; Sleep Initiation and Maintenance Disorders
PubMed: 37682445
DOI: 10.1007/s40266-023-01065-x -
Journal of Alzheimer's Disease : JAD 2022Plasma neuronal-derived extracellular vesicles (NDEV) contain proteins of pathological, diagnostic, and therapeutic relevance. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Plasma neuronal-derived extracellular vesicles (NDEV) contain proteins of pathological, diagnostic, and therapeutic relevance.
OBJECTIVE
We investigated the associations of six plasma NDEV markers with Alzheimer's disease (AD) severity, cognition and functioning, and changes in these biomarkers after Cerebrolysin®, donepezil, and a combination therapy in AD.
METHODS
Plasma NDEV levels of Aβ42, total tau, P-T181-tau, P-S393-tau, neurogranin, and REST were determined in: 1) 116 mild to advanced AD patients and in 20 control subjects; 2) 110 AD patients treated with Cerebrolysin®, donepezil, or combination therapy in a randomized clinical trial (RCT). Samples for NDEV determinations were obtained at baseline in the NDEV study and at baseline and study endpoint in the RCT. Cognition and functioning were assessed at the same time points.
RESULTS
NDEV levels of Aβ42, total tau, P-T181-tau, and P-S393-tau were higher and those of neurogranin and REST were lower in mild-to-moderate AD than in controls (p < 0.05 to p < 0.001). NDEV total tau, neurogranin, and REST increased with AD severity (p < 0.05 to p < 0.001). NDEV Aβ42 and P-T181-tau correlated negatively with serum BDNF (p < 0.05), and total-tau levels were associated to plasma TNF-α (p < 0.01) and cognitive impairment (p < 0.05). Combination therapy reduced NDEV Aβ42 with respect to monotherapies (p < 0.05); and NDEV total tau, P-T181-tau, and P-S396-tau were decreased in Cerebrolysin-treated patients compared to those on donepezil monotherapy (p < 0.05).
CONCLUSION
The present results demonstrate the utility of NDEV determinations of pathologic and synaptic proteins as effective AD biomarkers, as markers of AD severity, and as potential tools for monitoring the effects of anti-AD drugs.
Topics: Humans; Alzheimer Disease; Donepezil; Neurogranin; tau Proteins; Amyloid beta-Peptides; Cognitive Dysfunction; Biomarkers; Extracellular Vesicles; Peptide Fragments
PubMed: 36155516
DOI: 10.3233/JAD-220575